In-vivo cerebral artery pulsation assessment with Dynamic Computed Tomography Angiography

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Stam, Sabine M. L. Linden, René Aquarius, Alessa Hering, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3851165/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Four-Dimensional Computed Tomography Angiography (4D CTA) seems a promising technique for capturing vessel motion of cerebral arteries, which may help to assess pathological conditions such as intracranial aneurysms. The goal of our current study is to capture the lumen diameter of cerebral arteries during three subsequent cardiac cycles with 4D CTA and to assess vessel motion, anticipating consistent expansion patterns within each cardiac cycle. Eighteen adult patients with unruptured and untreated intracranial aneurysms were recruited at Radboud University Medical Center. Three cardiac cycles were captured, on a wide detector CT system, using ECG-gated 4D CTA. To reduce the impact of small head movements during the acquisition, a rigid-body registration was employed. Three 10 mm segments of cerebral arteries were selected. The total deformation of the vessel lumen was calculated using a deformable registration algorithm and was used as a substitute measure for vessel motion. No pulsations could be registered, which was probably caused by pulsation motion below threshold of detection in combination with insufficient Signal-to-Noise Ratio. Further studies need to investigate if large intracranial structures can be evaluated and if using a novel scanner with a high spatial resolution would result in reproducible measurements of arteries this size. Figures Figure 1 Figure 2 Figure 3 Introduction Information on vessel motion of cerebral arteries might help to assess pathophysiological conditions, such as intracranial aneurysms, [ 1 ] which could lead to valuable insights regarding the estimation of the aneurysm wall stability and possibly the risk of rupture. The exact movement patterns of the intracranial aneurysm wall is unknown and probably very complex as variations can occur between patients [ 2 ] and between cardiac cycles. A technique with both sufficient spatial and temporal resolution is required to visualize and quantify these extremely small pulsating motions of the intracranial aneurysm wall. Four-Dimensional Computed Tomography Angiography (4D CTA) seems a promising technique for capturing these movements, according to in vivo studies on patients with intracranial aneurysms, as described in a previously performed review. [ 3 ] Our previously performed in vitro study [ 4 ] showed reproducible measurements of pulsatile movements of an elastic tube for diameter changes exceeding 0.3 mm, captured with 4D CTA. This in vitro study also emphasized the significance of evaluating the heart rate, demonstrating that lower frequencies yield greater accuracy in comparison to those obtained at higher frequencies. The in vivo situation differs from an in vitro set-up in several ways, such as a decreased quality of the CT images (due to for example patient motion and artifacts) [ 5 ], the presence of biological and anatomical variation and the absence of a golden reference standard. Therefore, analyzing the vessel motion of cerebral arteries is deemed essential as the primary step prior to assessing the movement of intracranial aneurysm walls. It is expected that healthy cerebral arteries expand in a consistent way each cardiac cycle. This consistency can act as a surrogate for a reference standard: acquired 4D CTA data should look the same every cardiac cycle. Additionally, vessel motion of cerebral arteries should be less susceptible to random variations due to the absence of obvious vessel wall pathology as encountered in the intracranial aneurysm wall. The 10% cardiac-cycle related diameter change in the common carotid arteries [ 6 ], coupled with our previous in vitro experiment, suggests that 4D CTA has the ability to capture vessel movements of arteries with a diameter exceeding 3 mm. The goal of our current study is to capture the lumen diameter of cerebral arteries during three subsequent cardiac cycles with 4D CTA and to assess vessel motion, anticipating consistent expansion patterns within each cardiac cycle. Methods Study population Patients were recruited at Radboud University Medical Center between December 2020 and November 2021. Adult patients with at least one unruptured and untreated intracranial aneurysm with a scheduled follow-up were eligible for inclusion. Exclusion criteria were 1) contra-indications for CT or Iodinated contrast agent, 2) aged below 18 years 3) unable to give informed consent, 4) impaired kidney function or eGFR value < 60 ml/min/1.73m 2 . Patients eligible for inclusion were approached by their neurologist or neurosurgeon. Written informed consent was obtained from all subjects. After obtaining their written informed consent and agreement to participate, patient characteristics were extracted from the electronic medical records. This study and all experimental protocols were approved by the local medical research ethics committee (METC number: NL75245.091.20). This study is performed in accordance with the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations. The protocol was registered at the Internal Clinical Trials Registry Platform with the ID NL8936. Patient and 4D CTA characteristics The following patient characteristics were presented for each included patient: age, sex, hypertension, smoking, positive history of SAH, positive family history of IA, positive family history of Subarachnoid Hemorrhage (SAH), number of intracranial aneurysms (IA’s), heart rate, dose-length-product and effective dose. For each analyzed patient, the mean contrast intensity (in Hounsfield Units (HU)) within the vessel segment was determined, using an averaged mask, determined by region growing on the averaged volume of 10 time phases (0%, 10%,…,90%). The vessel diameter was determined by the volume of the averaged mask and the assumption that the vessel is cylindrical and has a length of 10 mm. 4D CTA acquisition and reconstruction ECG-gated 4D CTA scans were performed on a wide detector CT system ( CT Aquilion ONE Prism Edition, Canon Medical Systems, Otawara Japan ). A scan range of 4 to 8 cm including the aneurysm was selected. Seventy milliliters of iodinated contrast agent with a concentration of 300 mg/ml Iodine ( Iomeron 300®, Bracco Imaging Germany GmbH ) was injected intravenously and continuously during the scan at a speed of 5 ml/s. Scans were acquired with a tube voltage of 100 kV, tube current of 340 mA, and gantry rotation time of 0.275 s. The CT acquisition of three cardiac cycles was started at the R-peak of the simultaneously recorded ECG signal with 4 seconds delay after common carotid artery enhancement. The subjects received the instruction not to move during the acquisition. Per cardiac cycle, twenty datasets were reconstructed with retrospective ECG gating and the partial scanning algorithm, implying that each dataset represented a time phase of 5% of one cardiac cycle and using 180 degrees rotation for each time phase [ 7 ]. Reconstructions were made with Deep-Learning Based reconstruction (DLR) (AiCE Brain CTA, Canon Medical Systems) in full rotation mode with a Field Of View (FOV) diameter of 100 mm, and a slice thickness of 0.5 mm. This reconstruction algorithm was demonstrated to be optimal for this purpose in our previous phantom study.[ 8 ] The effective dose was estimated by multiplying the dose length product with 0.0021 mSv/mGy.cm.[ 9 ] Post Processing A rigid-body registration was employed to reduce the impact of small head movements during the acquisition of 4D CTA scans, using MevisLab ( Version 3.2a, MeVis Medical Solutions AG Bremen, Germany ). Detailed information about the rigid-body registration can be found in Appendix A: Head movement correction. Three arteries in each patient were selected by an experienced neuroradiologist, leading to subvolumes of the imaging dataset measuring 10 x 10 x 10 mm (Fig. 1 ). This resulted in artery segments with a length of approximately 10 mm. Vessel segments were excluded if they exhibited signs of vessel wall pathology (e.g. atherosclerosis) or major side branches. The specific arteries selected for each patient were as follows: Middle cerebral artery left (MCA left) Middle cerebral artery right (MCA right) Basilar artery (BA) The total deformation of the vessel lumen was used as a substitute measure for vessel motion within the subvolumes as described above. The deformation was determined with a deformable registration algorithm, using MevisLab ( Version 3.2a, MeVis Medical Solutions AG Bremen, Germany ). A detailed description of this registration method can be found in Appendix B: deformable registration. The volume change was defined as the total deformation of all voxels within the lumen. Outcome measures Diameter change pattern The relative volume change was converted to absolute diameter change, knowing the diameter of the vessel. The diameter change pattern of the three cardiac cycles was visualized. Both the similarity of the three cardiac cycles and the maximal diameter change was evaluated visually by the authors. Results Patient and 4D CTA characteristics Eighteen patients were included in the study, though 5 patients needed to be excluded. In two subjects, the raw CT data was stored incorrectly and in another subject only one cardiac cycle was captured by the CT scanner. In one subject, the contrast timing was not appropriately executed and in one subject an artefact (due to coils present in another treated intracranial aneurysm) made analysis of these vessels impossible. This led to a total of 13 patients for which three vessels each (MCA left, MCA right and BA) were analyzed. For one patient, the MCA left was excluded for analysis, due an existing aneurysm at this location. No segments were excluded because they exhibited signs of atherosclerosis. The patient and 4D CTA characteristics of the analyzed patients can be seen in Table 1 . In Appendix C: patient characteristics , characteristics of the entire study population, included and excluded, can be found. Table 1 Subject, 4D CTA and Intracranial Aneurysm (IA) Characteristics. SAH = Subarachnoid Hemorrhage, nr.=number of, bpm = beats per minute, mm = millimeter, HU = Hounsfield Units. *The hypertension status of one subject is unknown. Patient Mean ± std / (%) Analyzed patients (n = 13) Age [years] 63 ± 9 Male gender 7 (54%) Hypertension* 6 (50%) (n = 12) Smoking (current or former) 9 (69%) Positive history of SAH 3 (23%) Positive family history (IA) 0 (0%) Positive family history (SAH) 1 (8%) IA’s [nr.] 1 (77%), 2 (15%), 3 (8%) Heart rate [bpm] 75 ± 12 Dose-length-product [mGy*cm] 460 ± 75 Effective Dose [mSv] 0.97 ± 0.19 Basilar artery diameter [mm] 3.3 ± 0.76 MCA left diameter [mm] 2.7 ± 0.49 MCA right diameter [mm] 2.8 ± 0.45 Intensity basilar artery [HU] 437 ± 91 Intensity MCA left [HU] 432 ± 91 Intensity MCA right [HU] 436 ± 86 Maximal intensity difference between cardiac cycles [HU] 39 ± 19 In Fig. 2 , the mean intensity (HU) inside the basilar artery can be seen for each patient. Large differences can be observed between patients, ranging from 257 HU to 656 HU. Small difference can be observed between cardiac cycles within each patient (maximum difference of 76 HU between cardiac cycles). Diameter change pattern For all patients and all arteries, the captured maximum diameter change was below 0.3 mm. All diameter change patterns can be found in Appendix D: diameter change pattern . Visual comparison revealed a lack of similarity among three cardiac cycles. In Fig. 3 , six captured diameter change patterns are visualized. Patient 16 has a relatively low heart rate (62 bpm) and the diameters of both left and right MCA are larger than 3.0 mm, yet the diameter change pattern of the left and right MCA are dissimilar and well below the 0.3 mm threshold (Fig. 3 , panel a and b). Additionally, the four arteries with the largest diameter, each one from a different patient, are shown in Fig. 3 (panels c-f). We expected that these large arteries would lead to the largest vessel motions, which should be detectible. Discussion This study evaluated the volume changes of selected cerebral vessel segments over three cardiac cycles. We found that the captured vessel motion was below the detectable motion of 0.3 mm in all patients and is therefore indistinguishable from noise. Our previous in vitro study showed that 4D CTA on this type of CT scanner can be used to capture reproducible and reliable diameter changes exceeding 0.30 mm. [ 4 ] It was also concluded that the patient’s heart rate strongly influences the accuracy of the results. The assumed 10% diameter change in blood vessels, would mean that in arteries with a diameter exceeding 3 mm and a low heart rate, capturing reproducible volume change measurements should be possible. In our study, we did not find reproducible volume change measurements in the examined cerebral arteries. The lack of finding reproducible volume change measurements in our study could be related to several factors. Vessel wall motion might be too small to register for various reasons. First, the small size of the vessels, which was < 3 mm in 46% of the basilar artery, 54% of the left MCA and 69% for the right MCA. Second, a relatively high heart rate of 75 beats per minute on average in this cohort, which makes acquisition for diameter changes more challenging. Third, it is known that age is negatively corelated with vessel wall elasticity [ 8 ]; the mean age in our cohort is 63 years. However, even in young patients with larger vessels and a low heart rate (patient 16 or 13), no diameter changes were observed. [ 10 ] Fourth, it might also be the case that the assumption of an arterial, cardiac-cycle related diameter change 10% [ 6 ], was too optimistic. Another study [ 11 ] examined the pulsation pattern of the common carotid artery using 4D CTA and found that their automatic registration method was feasible. This study anticipated a mean diameter of the common carotid artery of 7.9 mm with a mean diameter change of 0.5 mm, which was measured with ultrasound in another study [ 12 ], which is only a vessel expansion of 6.3%. Acquisition of the relatively small vessel wall motion was further hampered by factors that were absent in our in vitro study and that introduced noise in the in vivo images. Examples of these factors are: patient motion and artifacts, [ 5 ] differences in contrast agent between cardiac cycles and between patients and differences due to biological variation between patients and between cardiac cycles, for example due to variation in cardiac output. Although we corrected for patient motion with our rigid-body registration, the other factors mentioned could not be addressed post-acquisition. When comparing our study to the literature on cerebral arteries, one other clinical study assessed the reproducibility between multiple pulsation cycles for intracranial aneurysms. [ 13 ] This study showed high reproducibility in measuring the maximum volume change per cardiac cycle, for aneurysms exceeding 5 mm, with variations of approximately 0.5 mm. It is essential to note that our study differs in scope as we comprehensively assessed the entire pulsation pattern, unlike this previous study which focused on the maximum volume change measurement. The variations of the cerebral arteries that we examined did not include vessels with a diameter > 5 mm and the smaller vessels that we examined resulted in non-reproducible measurements, which is in scope with this article. In a separate clinical study, one complete pulsation cycle was examined for 14 aneurysms with diameters ranging from 5 to 17 mm, the findings were that only 4 aneurysms showed a pulsation-like pattern. [ 1 ] Comparing to our study, we also find pulsation-like patterns. However, the reproducibility of these patterns was poor between cardiac cycles and thus these profiles were expected to be caused by other factors than pulsation. Our study has several strengths. The employed methodology for volume change measurements was based on the methods used in our in vitro study [ 4 ], where its efficacy was demonstrated. The results of this in vitro study were compared to the in vivo situation. Additionally, the focus of this study was on the dilation of cerebral vessels rather than aneurysms, as it is anticipated that these vessels expand uniformly and reproducibly for each cardiac cycle, in contrast to the greater uncertainty in movement of intracranial aneurysms, caused by for example blebs. [ 2 ] Thereby, three pulsation cycles were scanned and the full pulsation cycle was evaluated, in comparison to several in vivo studies, which only evaluated one pulsation cycle[ 1 ] [ 14 ] [ 15 ] [ 16 ] or only evaluated the maximal differences [ 13 ] [ 14 ] [ 15 ] [ 16 ]. In addition, the small movements of the patient is likely, therefore a dedicated motion correction was applied. This study has several limitations. Despite the knowledge that the heart rate influences the accuracy, the study included patients with heart rates ranging from 58 to 95 bpm. Administering heart rate-reducing medication could potentially lead to more accurate measurements. However, the patients who had a low heart rate in this study did not show detectable volume measurements. In addition, arteries were assumed to be cylindrical with a length of 10 mm in each subvolume for determination of the diameter change, which may not be exactly the case for some arteries. This could have led to a small over- or underestimation of the diameter change. The volumetric variation approach that was used in this study can only be used for a volume change as a whole and not be used to examine local diameter changes in cerebral arteries. Diameter change detection of cerebral vessels with a diameter of 2–5 mm was impossible, when using this 4D CTA scanner at conventional spatial resolution. However, more promising outcomes are anticipated for larger vessels or aneurysms, given that 4D CTA has previously demonstrated its capability to discern diameter changes in the aorta and common carotid artery. [ 11 ] [ 17 ] [ 18 ] [ 19 ] Further studies need to investigate if large intracranial structures, like large intracranial aneurysms, can be evaluated using our proposed methodology. The recent introduction of photon-counting or ultra-high resolution CT scanners offers the advantage of scanning with a spatial resolution approximately twice as high as the scanner used in our study. [ 20 ] This enhancement holds the potential to identify smaller diameter changes and, consequently, finer variations in intracranial aneurysms or arteries, although temporal resolution may remain a limiting factor. Conclusion This study evaluated the physiological cerebral artery pulsations using 4D CTA on a wide detector CT system. No pulsations could be registered for cerebral vessels with a diameter of 2–5 mm, which was probably caused by small motion of the cerebral vessel in combination with the insufficient signal-to-noise ratio associated with the measurements. Declarations Competing Interests F.J.A Meijer has a competing interest as a speaker for Canon medical system. This interest does not conflict with this study.The other authors declare that they do not have competing interests. Author Contribution L.B.S.: conceptualization, methodology, draft analysis, project administration, writing—review and editingS.M.L: conceptualization, methodology, final analysis, data curation, writing—original draft, visualization,R.A.: conceptualization, methodology, writing—review and editing,A.H.: methodology, validationL.J.O.: conceptualization, methodology, validationF.J.A.M: conceptualization, methodology, writing—review and editing, supervisionH.D.B: conceptualization, methodology, writing—review and editing, supervision Data availability The datasets generated and/or analysed during the current study are not publicly available due traceability to the individual subjects, despite the anonymization. Limited datasets may be available from the corresponding author on reasonable request. 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Beaussier, H., et al., Carotid plaque, arterial stiffness gradient, and remodeling in hypertension. Hypertension, 2008. 52 (4): p. 729-736. Dissaux, B., et al., Volume variation may be a relevant metric in the study of aneurysm pulsatility: a study using ECG-gated 4D-CTA (PULSAN). J Neurointerv Surg, 2020. 12 (6): p. 632-636. Kuroda, J., et al., Cardiac cycle-related volume change in unruptured cerebral aneurysms: a detailed volume quantification study using 4-dimensional CT angiography. Stroke, 2012. 43 (1): p. 61-6. Gu, Y., et al., Dynamic Volume Change Rate and Aspect Ratio Are Correlated to the Formation of an Irregular Morphology of Unruptured Intracranial Aneurysm. J Comput Assist Tomogr, 2019. 43 (2): p. 294-299. Illies, T., et al., Cerebral aneurysm pulsation: do iterative reconstruction methods improve measurement accuracy in vivo? AJNR Am J Neuroradiol, 2014. 35 (11): p. 2159-63. Weber, T.F., et al., Assessment of thoracic aortic conformational changes by four-dimensional computed tomography angiography in patients with chronic aortic dissection type b. European Radiology, 2009. 19 (1): p. 245-253. Zhang, J., et al., Large-Vessel Distensibility Measurement with Electrocardiographically Gated Multidetector CT: Phantom Study and Initial Experience. Radiology, 2007. 245 (1): p. 258-266. Ganten, M.-K., et al., Quantification of aortic distensibility in abdominal aortic aneurysm using ECG-gated multi-detector computed tomography. European Radiology, 2008. 18 (5): p. 966-973. van der Bie, J., et al., Photon-counting CT: Review of initial clinical results. Eur J Radiol, 2023. 163 : p. 110829. Additional Declarations Competing interest reported. F.J.A Meijer has a competing interest as a speaker for Canon medical system. This interest does not conflict with this study. The other authors declare that they do not have competing interests. Supplementary Files AppendixAHeadmovementcorrection.pdf AppendixBDeformableregistration.pdf AppendixCPatientcharacteristics.pdf AppendixDDiameterchangepattern.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3851165","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":267376830,"identity":"ba16c3a9-4f07-47e8-b267-c598b8af9b02","order_by":0,"name":"Lotte B. 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Oostveen","email":"","orcid":"","institution":"Radboud University Nijmegen Medical Centre","correspondingAuthor":false,"prefix":"","firstName":"Luuk","middleName":"J.","lastName":"Oostveen","suffix":""},{"id":267376835,"identity":"7992e0d1-7229-4db0-960d-691b29fbdd3d","order_by":5,"name":"Frederick J.A. Meijer","email":"","orcid":"","institution":"Radboud University Nijmegen Medical Centre","correspondingAuthor":false,"prefix":"","firstName":"Frederick","middleName":"J.A.","lastName":"Meijer","suffix":""},{"id":267376836,"identity":"2bdad860-c539-4c13-bb79-72ec81e20e2f","order_by":6,"name":"Hieronymus D. Boogaarts","email":"","orcid":"","institution":"Radboud University Nijmegen Medical Centre","correspondingAuthor":false,"prefix":"","firstName":"Hieronymus","middleName":"D.","lastName":"Boogaarts","suffix":""}],"badges":[],"createdAt":"2024-01-10 18:29:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3851165/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3851165/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49822405,"identity":"d7a4ed8d-c58d-48c4-9324-95dfab70f3b6","added_by":"auto","created_at":"2024-01-18 15:20:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":361749,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e2D visualization of 3D subvolumes (10 x 10 x 10 mm) for three arteries: axial plane of the MCA left (a), axial plane of the MCA right (b) and coronal plane of the basilar artery (c).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/278a4b39a56ceeb28c4626be.png"},{"id":49822404,"identity":"beba2ed5-8410-4a49-a19b-0c670deb23b3","added_by":"auto","created_at":"2024-01-18 15:20:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":38073,"visible":true,"origin":"","legend":"\u003cp\u003eMean intensity basilar artery in Hounsfield Units (HU).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/bd4af5ed7e7445643fef5583.png"},{"id":49822411,"identity":"619c0bff-9b16-4843-8096-238392a7e886","added_by":"auto","created_at":"2024-01-18 15:20:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":468858,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eDiameter change pattern of the MCA left (a) and right (b) of patient 16 and the basilar artery of patient 3 (c), patient 13 (d), patient 8 (e) and patient 10 (f). Heart Rate (HR), beats-per-minute (bpm), millimeter (mm)\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/2f0b57330d33ccb0ba8274e7.png"},{"id":53534092,"identity":"06cc2b01-bb1e-457d-beaf-10f0811b0f1e","added_by":"auto","created_at":"2024-03-27 07:07:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":802317,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/bc72df94-3429-4d8a-83e9-2717ddb55927.pdf"},{"id":49822406,"identity":"c92fba10-6994-4cff-9884-2d2cb6760a12","added_by":"auto","created_at":"2024-01-18 15:20:01","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":199406,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixAHeadmovementcorrection.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/e364f81dc53c45858bde8dc6.pdf"},{"id":49824422,"identity":"01359862-b338-407a-82fa-9ec5fdd13dd5","added_by":"auto","created_at":"2024-01-18 15:36:01","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":224130,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixBDeformableregistration.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/51027dcac7f8e730eec8f30b.pdf"},{"id":49822877,"identity":"d7d895ea-2080-4372-bf59-28243fa619a1","added_by":"auto","created_at":"2024-01-18 15:28:01","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":154291,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixCPatientcharacteristics.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/f192ea58c7c5853f3a2e766d.pdf"},{"id":49822876,"identity":"cabd6e22-cf9d-4d68-88aa-383a67318e21","added_by":"auto","created_at":"2024-01-18 15:28:01","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":1069776,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixDDiameterchangepattern.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3851165/v1/b89ed15bc5ba4131ba337528.pdf"}],"financialInterests":"Competing interest reported. F.J.A Meijer has a competing interest as a speaker for Canon medical system. This interest does not conflict with this study.\nThe other authors declare that they do not have competing interests.","formattedTitle":"In-vivo cerebral artery pulsation assessment with Dynamic Computed Tomography Angiography","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInformation on vessel motion of cerebral arteries might help to assess pathophysiological conditions, such as intracranial aneurysms, [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] which could lead to valuable insights regarding the estimation of the aneurysm wall stability and possibly the risk of rupture. The exact movement patterns of the intracranial aneurysm wall is unknown and probably very complex as variations can occur between patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and between cardiac cycles.\u003c/p\u003e \u003cp\u003eA technique with both sufficient spatial and temporal resolution is required to visualize and quantify these extremely small pulsating motions of the intracranial aneurysm wall. Four-Dimensional Computed Tomography Angiography (4D CTA) seems a promising technique for capturing these movements, according to in vivo studies on patients with intracranial aneurysms, as described in a previously performed review. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur previously performed in vitro study [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] showed reproducible measurements of pulsatile movements of an elastic tube for diameter changes exceeding 0.3 mm, captured with 4D CTA. This in vitro study also emphasized the significance of evaluating the heart rate, demonstrating that lower frequencies yield greater accuracy in comparison to those obtained at higher frequencies. The in vivo situation differs from an in vitro set-up in several ways, such as a decreased quality of the CT images (due to for example patient motion and artifacts) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], the presence of biological and anatomical variation and the absence of a golden reference standard.\u003c/p\u003e \u003cp\u003eTherefore, analyzing the vessel motion of cerebral arteries is deemed essential as the primary step prior to assessing the movement of intracranial aneurysm walls. It is expected that healthy cerebral arteries expand in a consistent way each cardiac cycle. This consistency can act as a surrogate for a reference standard: acquired 4D CTA data should look the same every cardiac cycle. Additionally, vessel motion of cerebral arteries should be less susceptible to random variations due to the absence of obvious vessel wall pathology as encountered in the intracranial aneurysm wall.\u003c/p\u003e \u003cp\u003eThe 10% cardiac-cycle related diameter change in the common carotid arteries [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], coupled with our previous in vitro experiment, suggests that 4D CTA has the ability to capture vessel movements of arteries with a diameter exceeding 3 mm. The goal of our current study is to capture the lumen diameter of cerebral arteries during three subsequent cardiac cycles with 4D CTA and to assess vessel motion, anticipating consistent expansion patterns within each cardiac cycle.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\"\u003e\n \u003ch2\u003eStudy population\u003c/h2\u003e\n \u003cp\u003ePatients were recruited at Radboud University Medical Center between December 2020 and November 2021. Adult patients with at least one unruptured and untreated intracranial aneurysm with a scheduled follow-up were eligible for inclusion. Exclusion criteria were 1) contra-indications for CT or Iodinated contrast agent, 2) aged below 18 years 3) unable to give informed consent, 4) impaired kidney function or eGFR value\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. Patients eligible for inclusion were approached by their neurologist or neurosurgeon. Written informed consent was obtained from all subjects. After obtaining their written informed consent and agreement to participate, patient characteristics were extracted from the electronic medical records.\u003c/p\u003e\n \u003cp\u003eThis study and all experimental protocols were approved by the local medical research ethics committee (METC number: NL75245.091.20). This study is performed in accordance with the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations. The protocol was registered at the Internal Clinical Trials Registry Platform with the ID NL8936.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\"\u003e\n \u003ch2\u003ePatient and 4D CTA characteristics\u003c/h2\u003e\n \u003cp\u003eThe following patient characteristics were presented for each included patient: age, sex, hypertension, smoking, positive history of SAH, positive family history of IA, positive family history of Subarachnoid Hemorrhage (SAH), number of intracranial aneurysms (IA\u0026rsquo;s), heart rate, dose-length-product and effective dose. For each analyzed patient, the mean contrast intensity (in Hounsfield Units (HU)) within the vessel segment was determined, using an averaged mask, determined by region growing on the averaged volume of 10 time phases (0%, 10%,\u0026hellip;,90%). The vessel diameter was determined by the volume of the averaged mask and the assumption that the vessel is cylindrical and has a length of 10 mm.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\"\u003e\n \u003ch2\u003e4D CTA acquisition and reconstruction\u003c/h2\u003e\n \u003cp\u003eECG-gated 4D CTA scans were performed on a wide detector CT system (\u003cem\u003eCT Aquilion ONE Prism Edition, Canon Medical Systems, Otawara Japan\u003c/em\u003e). A scan range of 4 to 8 cm including the aneurysm was selected. Seventy milliliters of iodinated contrast agent with a concentration of 300 mg/ml Iodine (\u003cem\u003eIomeron 300\u0026reg;, Bracco Imaging Germany GmbH\u003c/em\u003e) was injected intravenously and continuously during the scan at a speed of 5 ml/s. Scans were acquired with a tube voltage of 100 kV, tube current of 340 mA, and gantry rotation time of 0.275 s. The CT acquisition of three cardiac cycles was started at the R-peak of the simultaneously recorded ECG signal with 4 seconds delay after common carotid artery enhancement. The subjects received the instruction not to move during the acquisition.\u003c/p\u003e\n \u003cp\u003ePer cardiac cycle, twenty datasets were reconstructed with retrospective ECG gating and the partial scanning algorithm, implying that each dataset represented a time phase of 5% of one cardiac cycle and using 180 degrees rotation for each time phase [\u003cspan\u003e7\u003c/span\u003e]. Reconstructions were made with Deep-Learning Based reconstruction (DLR) \u003cem\u003e(AiCE Brain CTA, Canon Medical Systems)\u003c/em\u003e in full rotation mode with a Field Of View (FOV) diameter of 100 mm, and a slice thickness of 0.5 mm. This reconstruction algorithm was demonstrated to be optimal for this purpose in our previous phantom study.[\u003cspan\u003e8\u003c/span\u003e] The effective dose was estimated by multiplying the dose length product with 0.0021 mSv/mGy.cm.[\u003cspan\u003e9\u003c/span\u003e]\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003ePost Processing\u003c/h2\u003e\n \u003cp\u003eA rigid-body registration was employed to reduce the impact of small head movements during the acquisition of 4D CTA scans, using MevisLab (\u003cem\u003eVersion 3.2a, MeVis Medical Solutions AG Bremen, Germany\u003c/em\u003e). Detailed information about the rigid-body registration can be found in \u003cspan type=\"Underline\" name=\"Emphasis\"\u003eAppendix A: Head movement correction.\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003eThree arteries in each patient were selected by an experienced neuroradiologist, leading to subvolumes of the imaging dataset measuring 10 x 10 x 10 mm (Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). This resulted in artery segments with a length of approximately 10 mm. Vessel segments were excluded if they exhibited signs of vessel wall pathology (e.g. atherosclerosis) or major side branches. The specific arteries selected for each patient were as follows:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eMiddle cerebral artery left (MCA left)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eMiddle cerebral artery right (MCA right)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eBasilar artery (BA)\u003c/p\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n \u003cdiv\u003eThe total deformation of the vessel lumen was used as a substitute measure for vessel motion within the subvolumes as described above. The deformation was determined with a deformable registration algorithm, using MevisLab (\u003cem\u003eVersion 3.2a, MeVis Medical Solutions AG Bremen, Germany\u003c/em\u003e). A detailed description of this registration method can be found in \u003cspan type=\"Underline\" name=\"Emphasis\"\u003eAppendix B: deformable registration.\u003c/span\u003e The volume change was defined as the total deformation of all voxels within the lumen.\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003eOutcome measures\u003c/h2\u003e\n \u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eDiameter change pattern\u003c/h2\u003e\n \u003cp\u003eThe relative volume change was converted to absolute diameter change, knowing the diameter of the vessel. The diameter change pattern of the three cardiac cycles was visualized. Both the similarity of the three cardiac cycles and the maximal diameter change was evaluated visually by the authors.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003ePatient and 4D CTA characteristics\u003c/h2\u003e\n \u003cp\u003eEighteen patients were included in the study, though 5 patients needed to be excluded. In two subjects, the raw CT data was stored incorrectly and in another subject only one cardiac cycle was captured by the CT scanner. In one subject, the contrast timing was not appropriately executed and in one subject an artefact (due to coils present in another treated intracranial aneurysm) made analysis of these vessels impossible. This led to a total of 13 patients for which three vessels each (MCA left, MCA right and BA) were analyzed. For one patient, the MCA left was excluded for analysis, due an existing aneurysm at this location. No segments were excluded because they exhibited signs of atherosclerosis. The patient and 4D CTA characteristics of the analyzed patients can be seen in Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e. In \u003cspan type=\"Underline\" name=\"Emphasis\"\u003eAppendix C: patient characteristics\u003c/span\u003e, characteristics of the entire study population, included and excluded, can be found.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eSubject, 4D CTA and Intracranial Aneurysm (IA) Characteristics. SAH\u0026thinsp;=\u0026thinsp;Subarachnoid Hemorrhage, nr.=number of, bpm\u0026thinsp;=\u0026thinsp;beats per minute, mm\u0026thinsp;=\u0026thinsp;millimeter, HU\u0026thinsp;=\u0026thinsp;Hounsfield Units. *The hypertension status of one subject is unknown.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;std / (%)\u003c/p\u003e\n \u003cp\u003eAnalyzed patients (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge [years]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale gender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (50%) (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking (current or former)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive history of SAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive family history (IA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive family history (SAH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIA\u0026rsquo;s [nr.]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (77%), 2 (15%), 3 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart rate [bpm]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDose-length-product [mGy*cm]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e460\u0026thinsp;\u0026plusmn;\u0026thinsp;75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEffective Dose [mSv]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasilar artery diameter [mm]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCA left diameter [mm]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCA right diameter [mm]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntensity basilar artery [HU]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e437\u0026thinsp;\u0026plusmn;\u0026thinsp;91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntensity MCA left [HU]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e432\u0026thinsp;\u0026plusmn;\u0026thinsp;91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntensity MCA right [HU]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e436\u0026thinsp;\u0026plusmn;\u0026thinsp;86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximal intensity difference between cardiac cycles [HU]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eIn Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e, the mean intensity (HU) inside the basilar artery can be seen for each patient. Large differences can be observed between patients, ranging from 257 HU to 656 HU. Small difference can be observed between cardiac cycles within each patient (maximum difference of 76 HU between cardiac cycles).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003eDiameter change pattern\u003c/h2\u003e\n \u003cp\u003eFor all patients and all arteries, the captured maximum diameter change was below 0.3 mm. All diameter change patterns can be found in \u003cspan type=\"Underline\" name=\"Emphasis\"\u003eAppendix D: diameter change pattern\u003c/span\u003e. Visual comparison revealed a lack of similarity among three cardiac cycles. In Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e, six captured diameter change patterns are visualized. Patient 16 has a relatively low heart rate (62 bpm) and the diameters of both left and right MCA are larger than 3.0 mm, yet the diameter change pattern of the left and right MCA are dissimilar and well below the 0.3 mm threshold (Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e, panel a and b). Additionally, the four arteries with the largest diameter, each one from a different patient, are shown in Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e (panels c-f). We expected that these large arteries would lead to the largest vessel motions, which should be detectible.\u003c/p\u003e\n \u003cdiv\u003e\u003cbr\u003e\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated the volume changes of selected cerebral vessel segments over three cardiac cycles. We found that the captured vessel motion was below the detectable motion of 0.3 mm in all patients and is therefore indistinguishable from noise.\u003c/p\u003e \u003cp\u003eOur previous in vitro study showed that 4D CTA on this type of CT scanner can be used to capture reproducible and reliable diameter changes exceeding 0.30 mm. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] It was also concluded that the patient\u0026rsquo;s heart rate strongly influences the accuracy of the results. The assumed 10% diameter change in blood vessels, would mean that in arteries with a diameter exceeding 3 mm and a low heart rate, capturing reproducible volume change measurements should be possible. In our study, we did not find reproducible volume change measurements in the examined cerebral arteries.\u003c/p\u003e \u003cp\u003eThe lack of finding reproducible volume change measurements in our study could be related to several factors. Vessel wall motion might be too small to register for various reasons. First, the small size of the vessels, which was \u0026lt;\u0026thinsp;3 mm in 46% of the basilar artery, 54% of the left MCA and 69% for the right MCA. Second, a relatively high heart rate of 75 beats per minute on average in this cohort, which makes acquisition for diameter changes more challenging. Third, it is known that age is negatively corelated with vessel wall elasticity [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]; the mean age in our cohort is 63 years. However, even in young patients with larger vessels and a low heart rate (patient 16 or 13), no diameter changes were observed. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Fourth, it might also be the case that the assumption of an arterial, cardiac-cycle related diameter change 10% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], was too optimistic. Another study [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] examined the pulsation pattern of the common carotid artery using 4D CTA and found that their automatic registration method was feasible. This study anticipated a mean diameter of the common carotid artery of 7.9 mm with a mean diameter change of 0.5 mm, which was measured with ultrasound in another study [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], which is only a vessel expansion of 6.3%.\u003c/p\u003e \u003cp\u003eAcquisition of the relatively small vessel wall motion was further hampered by factors that were absent in our in vitro study and that introduced noise in the in vivo images. Examples of these factors are: patient motion and artifacts, [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] differences in contrast agent between cardiac cycles and between patients and differences due to biological variation between patients and between cardiac cycles, for example due to variation in cardiac output. Although we corrected for patient motion with our rigid-body registration, the other factors mentioned could not be addressed post-acquisition.\u003c/p\u003e \u003cp\u003eWhen comparing our study to the literature on cerebral arteries, one other clinical study assessed the reproducibility between multiple pulsation cycles for intracranial aneurysms. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] This study showed high reproducibility in measuring the maximum volume change per cardiac cycle, for aneurysms exceeding 5 mm, with variations of approximately 0.5 mm. It is essential to note that our study differs in scope as we comprehensively assessed the entire pulsation pattern, unlike this previous study which focused on the maximum volume change measurement. The variations of the cerebral arteries that we examined did not include vessels with a diameter\u0026thinsp;\u0026gt;\u0026thinsp;5 mm and the smaller vessels that we examined resulted in non-reproducible measurements, which is in scope with this article. In a separate clinical study, one complete pulsation cycle was examined for 14 aneurysms with diameters ranging from 5 to 17 mm, the findings were that only 4 aneurysms showed a pulsation-like pattern. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Comparing to our study, we also find pulsation-like patterns. However, the reproducibility of these patterns was poor between cardiac cycles and thus these profiles were expected to be caused by other factors than pulsation.\u003c/p\u003e \u003cp\u003eOur study has several strengths. The employed methodology for volume change measurements was based on the methods used in our in vitro study [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], where its efficacy was demonstrated. The results of this in vitro study were compared to the in vivo situation. Additionally, the focus of this study was on the dilation of cerebral vessels rather than aneurysms, as it is anticipated that these vessels expand uniformly and reproducibly for each cardiac cycle, in contrast to the greater uncertainty in movement of intracranial aneurysms, caused by for example blebs. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Thereby, three pulsation cycles were scanned and the full pulsation cycle was evaluated, in comparison to several in vivo studies, which only evaluated one pulsation cycle[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] or only evaluated the maximal differences [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In addition, the small movements of the patient is likely, therefore a dedicated motion correction was applied.\u003c/p\u003e \u003cp\u003eThis study has several limitations. Despite the knowledge that the heart rate influences the accuracy, the study included patients with heart rates ranging from 58 to 95 bpm. Administering heart rate-reducing medication could potentially lead to more accurate measurements. However, the patients who had a low heart rate in this study did not show detectable volume measurements. In addition, arteries were assumed to be cylindrical with a length of 10 mm in each subvolume for determination of the diameter change, which may not be exactly the case for some arteries. This could have led to a small over- or underestimation of the diameter change. The volumetric variation approach that was used in this study can only be used for a volume change as a whole and not be used to examine local diameter changes in cerebral arteries.\u003c/p\u003e \u003cp\u003eDiameter change detection of cerebral vessels with a diameter of 2\u0026ndash;5 mm was impossible, when using this 4D CTA scanner at conventional spatial resolution. However, more promising outcomes are anticipated for larger vessels or aneurysms, given that 4D CTA has previously demonstrated its capability to discern diameter changes in the aorta and common carotid artery. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Further studies need to investigate if large intracranial structures, like large intracranial aneurysms, can be evaluated using our proposed methodology. The recent introduction of photon-counting or ultra-high resolution CT scanners offers the advantage of scanning with a spatial resolution approximately twice as high as the scanner used in our study. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] This enhancement holds the potential to identify smaller diameter changes and, consequently, finer variations in intracranial aneurysms or arteries, although temporal resolution may remain a limiting factor.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study evaluated the physiological cerebral artery pulsations using 4D CTA on a wide detector CT system. No pulsations could be registered for cerebral vessels with a diameter of 2\u0026ndash;5 mm, which was probably caused by small motion of the cerebral vessel in combination with the insufficient signal-to-noise ratio associated with the measurements.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003cp\u003eF.J.A Meijer has a competing interest as a speaker for Canon medical system. This interest does not conflict with this study.The other authors declare that they do not have competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.B.S.: conceptualization, methodology, draft analysis, project administration, writing\u0026mdash;review and editingS.M.L: conceptualization, methodology, final analysis, data curation, writing\u0026mdash;original draft, visualization,R.A.: conceptualization, methodology, writing\u0026mdash;review and editing,A.H.: methodology, validationL.J.O.: conceptualization, methodology, validationF.J.A.M: conceptualization, methodology, writing\u0026mdash;review and editing, supervisionH.D.B: conceptualization, methodology, writing\u0026mdash;review and editing, supervision\u003c/p\u003e\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due traceability to the individual subjects, despite the anonymization. Limited datasets may be available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIllies, T., et al., \u003cem\u003eFeasibility of Quantification of Intracranial Aneurysm Pulsation with 4D CTA with Manual and Computer-Aided Post-Processing.\u003c/em\u003e PLOS ONE, 2016. \u003cstrong\u003e11\u003c/strong\u003e(11): p. e0166810.\u003c/li\u003e\n\u003cli\u003eAshkezari, S.F.S., et al., \u003cem\u003eHemodynamics in aneurysm blebs with different wall characteristics.\u003c/em\u003e Journal of NeuroInterventional Surgery, 2021. \u003cstrong\u003e13\u003c/strong\u003e(7): p. 642-646.\u003c/li\u003e\n\u003cli\u003eStam, L.B., et al., \u003cem\u003eA review on imaging techniques and quantitative measurements for dynamic imaging of cerebral aneurysm pulsations.\u003c/em\u003e Scientific Reports, 2021. \u003cstrong\u003e11\u003c/strong\u003e(1): p. 2175.\u003c/li\u003e\n\u003cli\u003eLinden, S.M.L., et al., \u003cem\u003eCapturing vessel wall motion with Dynamic Computed Tomography Angiography: a phantom study to determine spatial and temporal resolution boundaries.\u003c/em\u003e under review, 2023.\u003c/li\u003e\n\u003cli\u003eDiwakar, M. and M. Kumar, \u003cem\u003eA review on CT image noise and its denoising.\u003c/em\u003e Biomedical Signal Processing and Control, 2018. \u003cstrong\u003e42\u003c/strong\u003e: p. 73-88.\u003c/li\u003e\n\u003cli\u003eHansen, F., et al., \u003cem\u003eNon-invasive measurement of pulsatile vessel diameter change and elastic properties in human arteries: a methodological study.\u003c/em\u003e Clin Physiol, 1993. \u003cstrong\u003e13\u003c/strong\u003e(6): p. 631-43.\u003c/li\u003e\n\u003cli\u003eDesjardins, B. and E.A. Kazerooni, \u003cem\u003eECG-Gated Cardiac CT.\u003c/em\u003e American Journal of Roentgenology, 2004. \u003cstrong\u003e182\u003c/strong\u003e(4): p. 993-1010.\u003c/li\u003e\n\u003cli\u003eStam, L.B., et al., \u003cem\u003eDynamic Computed Tomography Angiography for capturing vessel wall motion: a phantom study for optimal image reconstruction.\u003c/em\u003e PLOS ONE, accepted, 2023.\u003c/li\u003e\n\u003cli\u003eValentin, J., \u003cem\u003eManaging patient dose in multi-detector computed tomography(MDCT). ICRP Publication 102.\u003c/em\u003e Ann ICRP, 2007. \u003cstrong\u003e37\u003c/strong\u003e(1): p. 1-79, iii.\u003c/li\u003e\n\u003cli\u003eHansen, F., et al., \u003cem\u003eDiameter and compliance in the human common carotid artery--variations with age and sex.\u003c/em\u003e Ultrasound Med Biol, 1995. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 1-9.\u003c/li\u003e\n\u003cli\u003eHameeteman, K., et al., \u003cem\u003eAutomatic carotid artery distensibility measurements from CTA using nonrigid registration.\u003c/em\u003e Medical Image Analysis, 2013. \u003cstrong\u003e17\u003c/strong\u003e(5): p. 515-524.\u003c/li\u003e\n\u003cli\u003eBeaussier, H., et al., \u003cem\u003eCarotid plaque, arterial stiffness gradient, and remodeling in hypertension.\u003c/em\u003e Hypertension, 2008. \u003cstrong\u003e52\u003c/strong\u003e(4): p. 729-736.\u003c/li\u003e\n\u003cli\u003eDissaux, B., et al., \u003cem\u003eVolume variation may be a relevant metric in the study of aneurysm pulsatility: a study using ECG-gated 4D-CTA (PULSAN).\u003c/em\u003e J Neurointerv Surg, 2020. \u003cstrong\u003e12\u003c/strong\u003e(6): p. 632-636.\u003c/li\u003e\n\u003cli\u003eKuroda, J., et al., \u003cem\u003eCardiac cycle-related volume change in unruptured cerebral aneurysms: a detailed volume quantification study using 4-dimensional CT angiography.\u003c/em\u003e Stroke, 2012. \u003cstrong\u003e43\u003c/strong\u003e(1): p. 61-6.\u003c/li\u003e\n\u003cli\u003eGu, Y., et al., \u003cem\u003eDynamic Volume Change Rate and Aspect Ratio Are Correlated to the Formation of an Irregular Morphology of Unruptured Intracranial Aneurysm.\u003c/em\u003e J Comput Assist Tomogr, 2019. \u003cstrong\u003e43\u003c/strong\u003e(2): p. 294-299.\u003c/li\u003e\n\u003cli\u003eIllies, T., et al., \u003cem\u003eCerebral aneurysm pulsation: do iterative reconstruction methods improve measurement accuracy in vivo?\u003c/em\u003e AJNR Am J Neuroradiol, 2014. \u003cstrong\u003e35\u003c/strong\u003e(11): p. 2159-63.\u003c/li\u003e\n\u003cli\u003eWeber, T.F., et al., \u003cem\u003eAssessment of thoracic aortic conformational changes by four-dimensional computed tomography angiography in patients with chronic aortic dissection type b.\u003c/em\u003e European Radiology, 2009. \u003cstrong\u003e19\u003c/strong\u003e(1): p. 245-253.\u003c/li\u003e\n\u003cli\u003eZhang, J., et al., \u003cem\u003eLarge-Vessel Distensibility Measurement with Electrocardiographically Gated Multidetector CT: Phantom Study and Initial Experience.\u003c/em\u003e Radiology, 2007. \u003cstrong\u003e245\u003c/strong\u003e(1): p. 258-266.\u003c/li\u003e\n\u003cli\u003eGanten, M.-K., et al., \u003cem\u003eQuantification of aortic distensibility in abdominal aortic aneurysm using ECG-gated multi-detector computed tomography.\u003c/em\u003e European Radiology, 2008. \u003cstrong\u003e18\u003c/strong\u003e(5): p. 966-973.\u003c/li\u003e\n\u003cli\u003evan der Bie, J., et al., \u003cem\u003ePhoton-counting CT: Review of initial clinical results.\u003c/em\u003e Eur J Radiol, 2023. \u003cstrong\u003e163\u003c/strong\u003e: p. 110829.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3851165/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3851165/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eFour-Dimensional Computed Tomography Angiography (4D CTA) seems a promising technique for capturing vessel motion of cerebral arteries, which may help to assess pathological conditions such as intracranial aneurysms. The goal of our current study is to capture the lumen diameter of cerebral arteries during three subsequent cardiac cycles with 4D CTA and to assess vessel motion, anticipating consistent expansion patterns within each cardiac cycle.\u003c/p\u003e \u003cp\u003eEighteen adult patients with unruptured and untreated intracranial aneurysms were recruited at Radboud University Medical Center. Three cardiac cycles were captured, on a wide detector CT system, using ECG-gated 4D CTA. To reduce the impact of small head movements during the acquisition, a rigid-body registration was employed. Three 10 mm segments of cerebral arteries were selected. The total deformation of the vessel lumen was calculated using a deformable registration algorithm and was used as a substitute measure for vessel motion.\u003c/p\u003e \u003cp\u003eNo pulsations could be registered, which was probably caused by pulsation motion below threshold of detection in combination with insufficient Signal-to-Noise Ratio. Further studies need to investigate if large intracranial structures can be evaluated and if using a novel scanner with a high spatial resolution would result in reproducible measurements of arteries this size.\u003c/p\u003e","manuscriptTitle":"In-vivo cerebral artery pulsation assessment with Dynamic Computed Tomography Angiography","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 15:19:56","doi":"10.21203/rs.3.rs-3851165/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a43a4528-3378-4de4-bc14-b239698fd351","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-27T06:59:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 15:19:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3851165","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3851165","identity":"rs-3851165","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}